Coronary heart disease (CHD) is the leading cause of death worldwide for both genders, especially in high and middle-income countries. It has been intrinsically associated with atherosclerosis since the beginning of the 20th century. Pathologically, atherosclerosis is characterized by the formation of localized plaques within arterial walls which hinder normal blood flow. When atherosclerotic plaques are localized in one or more coronary arteries—known as coronary artery disease (CAD)—they prevent sufficient flow of oxygenated blood to the heart muscles. This results in an ischemic state at the heart muscle causing symptomatic events that range from angina pectoris to myocardial infarction, which ultimately result in sudden death.
For a long time, coronary artery bypass graft (CABG) remained the gold standard practice for the treatent of coronary artery disease. However, CABG involves an invasive intervention in order to bypass blocked artery using a graft harvested from other body parts. In 1977, the first percutaneous transluminal coronary angioplasty (PTCA) was performed to replace CABG as a minimally invasive technique, which spares CAD patients post-surgical risks and complications. With plain balloon angioplasty, it was noticed that post-procedural arterial response involved 5% risk of acute restenosis during the first 24 hours, or 20-50% risk of late occlusion during the first six months, due to elastic recoiling of arterial smooth muscles. Accordingly, placement of intracoronary stents became rapidly the method of choice for PTCA to act as a residing scaffold preventing arterial collapse incurred by plain balloon angioplasty. Furthermore, drug eluting stents were introduced to avoid neointimal hyperplasia caused by Bare Metal Stents (BMS). They decreased vessel restenosis rates from 20-30% with BMS to below 10-18%, revolutionizing the field of coronary intervention. By 2006, 8 out of 10 deployed coronary stents were DES, at an annual cost between 4 billion to 5 billion USD. Clinical evaluations have so far showed strong evidence of DES superiority over BMS in reduction of in-stent restenosis rates. However, cases of serious clinical events have raised concerns over DES long time safety and efficiency. In particular, risks of late and very late stent thrombosis. Several proposals have been offered to explain why such technical marvels would turn to be thrombogenic. Some of the most supported reasons are; 1) delayed endothelialization due to locally delivered cytotoxic or cytostatic drugs or other pathological risk factors, 2) inherent thrombogenicity of the stent as a foreign body to blood circulation, 3) hypersensitivity reactions related to the metallic material used for stent manufacturing or/and polymeric coatings used as drug carriers, 4) Dual Antiplatelet Therapy (DAPT) early discontinuation, and 5) stent malapposition or incomplete apposition, related to technical deployment.
A wide range of different materials have been previously used in the manufacturing of stents. These materials need to fulfill rigorous mechanical, physical and, chemical properties. According to procedure of implantation, long term application and safety, these properties are strongly studied and directly affect the choice of the stent. Titanium (Ti) and its alloys have been widely used in biomedical field especially in dental and orthopedic applications. They show excellent biocompatibility and high corrosion resistance due to the oxide layer formed on their surface, which is highly stable. However, for coronary stent manufactory, Ti application has been limited to bio-inert coatings that showed significantly reduced thrombogenicity and intimal hyperplasia, such as Ti-nitride-oxide layer on Titan© stent (Hexacath, France). The reason why pure titanium or some of its common alloys have not been used as stent materials is due to their high yield strength and relatively low tensile strength. Therefore, during deployment with balloon expansion, they will need to expand to stresses greater than their yield strength. Also, with the low tensile strength and low ductility, the stent will be easily prone to fracture. Alloying Ti with materials that would reduce its yield strength might be a good strategy to make it mechanically acceptable, while keeping original tensile strength. Some of the promising Ti-alloys for making stents are those containing Ta and Ni. Also, Ni—Ti alloys are extensively used in stents manufacturing, specially for self-expandabe stents. However, Ni-hypersensitivity and toxicity have stimulated the development of Ni-free Ti-based shape memory alloys.
Coatings have been initially used to enhance the biocompatibility of stent materials within vascular environment. Later, they were used as vehicle for drug loading and a platform to offer advanced solution for better endothelialization. However, using a different materials for coating, whether polymeric or metallic, can add a layer of complexity within the manufacturing process and more importantly can be mechanically questionable during application. Mechanical disturbance at the interface between the coating and substrate can occur due to crystal mismatch.
What is needed is a nanoarchitecture that is self-grown on a newly designed Ni-free alloy for DES surface treatment, that have mechanical properties that are comparable to Nitinol, which is currently the most widely used material for self-exandable stents, and has enhanced surface self-grown from the substrate material to avoid surface coating and crystal mismatch.